Trial Outcomes & Findings for Study to Evaluate Equivalence of Estradiol Vaginal Cream 0.01% to Estrace® Cream 0.01% in Atrophic Vaginitis (NCT NCT03294538)

Last Updated: 2019-12-26

Results Overview

Treatment comparison of the number of participants in the PP population that were identified as responders at the end of the treatment period evaluated on Day 8 + 1 is presented. A responder was defined as a participant with at least a 25% reduction from baseline in the sum of percent basal/parabasal + percent intermediate cells on vaginal cytology and vaginal pH ≤5.0 with a change from baseline vaginal pH of at least 0.5. Any participant who withdrew from the study because of lack of efficacy was included as a non-responder.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

663 participants

Primary outcome timeframe

Up to Day 9

Results posted on

2019-12-26

Participant Flow

The populations for this study included the Safety Population, the modified Intent-to-Treat (mITT) population, and the Per-Protocol (PP) Population.

Following the 14-day screening period, participants who continued to meet the inclusion/exclusion (I/E) criteria were randomly assigned to treatment on a 2:2:1 ratio of generic Estradiol Vaginal Cream United States Pharmacopoeia (USP), 0.01%; Estrace Vaginal Cream USP, 0.01%; or vehicle vaginal cream.

Participant milestones

Participant milestones
Measure	Generic Estradiol Vaginal Cream USP, 0.01% Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Overall Study STARTED	268	262	133
Overall Study Safety Population	267	262	132
Overall Study mITT Population	267	262	132
Overall Study PP Population	244	227	126
Overall Study COMPLETED	263	257	131
Overall Study NOT COMPLETED	5	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Generic Estradiol Vaginal Cream USP, 0.01% Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Overall Study Adverse Event	0	1	1
Overall Study Lost to Follow-up	1	0	0
Overall Study Outside of Visit Window	4	4	1

Baseline Characteristics

All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable basal/parabasal cells data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=267 Participants Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=262 Participants Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream n=132 Participants Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.	Total n=661 Participants Total of all reporting groups
Age, Continuous	59.5 Years STANDARD_DEVIATION 6.4 • n=267 Participants	59.5 Years STANDARD_DEVIATION 6.5 • n=262 Participants	60.8 Years STANDARD_DEVIATION 5.6 • n=132 Participants	59.9 Years STANDARD_DEVIATION 6.2 • n=661 Participants
Sex: Female, Male Female	267 Participants n=267 Participants	262 Participants n=262 Participants	132 Participants n=132 Participants	661 Participants n=661 Participants
Sex: Female, Male Male	0 Participants n=267 Participants	0 Participants n=262 Participants	0 Participants n=132 Participants	0 Participants n=661 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	79 Participants n=267 Participants	88 Participants n=262 Participants	42 Participants n=132 Participants	209 Participants n=661 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	188 Participants n=267 Participants	174 Participants n=262 Participants	90 Participants n=132 Participants	452 Participants n=661 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=267 Participants	0 Participants n=262 Participants	0 Participants n=132 Participants	0 Participants n=661 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=267 Participants	1 Participants n=262 Participants	0 Participants n=132 Participants	3 Participants n=661 Participants
Race (NIH/OMB) Asian	5 Participants n=267 Participants	3 Participants n=262 Participants	0 Participants n=132 Participants	8 Participants n=661 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=267 Participants	0 Participants n=262 Participants	0 Participants n=132 Participants	0 Participants n=661 Participants
Race (NIH/OMB) Black or African American	25 Participants n=267 Participants	24 Participants n=262 Participants	10 Participants n=132 Participants	59 Participants n=661 Participants
Race (NIH/OMB) White	235 Participants n=267 Participants	232 Participants n=262 Participants	121 Participants n=132 Participants	588 Participants n=661 Participants
Race (NIH/OMB) More than one race	0 Participants n=267 Participants	2 Participants n=262 Participants	1 Participants n=132 Participants	3 Participants n=661 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=267 Participants	0 Participants n=262 Participants	0 Participants n=132 Participants	0 Participants n=661 Participants
Percent of Basal/Parabasal Cells	34.4 percent of cells STANDARD_DEVIATION 35.1 • n=266 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable basal/parabasal cells data.	31.5 percent of cells STANDARD_DEVIATION 34.8 • n=262 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable basal/parabasal cells data.	36.3 percent of cells STANDARD_DEVIATION 34.3 • n=132 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable basal/parabasal cells data.	34.1 percent of cells STANDARD_DEVIATION 34.7 • n=660 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable basal/parabasal cells data.
Percent of Intermediate Cells	64.7 percent of cells STANDARD_DEVIATION 34.5 • n=266 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable intermediate cells data.	67.5 percent of cells STANDARD_DEVIATION 34.3 • n=262 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable intermediate cells data.	62.8 percent of cells STANDARD_DEVIATION 33.9 • n=132 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable intermediate cells data.	65 percent of cells STANDARD_DEVIATION 34.2 • n=660 Participants • All participants who were randomized and administered at least 1 dose of study drug (Safety Population) and with evaluable intermediate cells data.
Vaginal pH	6.2 pH STANDARD_DEVIATION 0.8 • n=267 Participants	6.2 pH STANDARD_DEVIATION 0.8 • n=262 Participants	6.1 pH STANDARD_DEVIATION 0.7 • n=132 Participants	6.2 pH STANDARD_DEVIATION 0.8 • n=661 Participants

PRIMARY outcome

Timeframe: Up to Day 9

Population: Participants who met I/E criteria, didn't develop a concurrent vaginal infection, completed Day 8 visit, and took 6-8 doses and didn't miss \>1 dose of study drug (PP Population). As pre-specified in the protocol, only the active groups (Generic Estradiol Vaginal Cream USP, 0.01% and Estrace Vaginal Cream USP, 0.01%) were included in this analysis.

Outcome measures

Outcome measures
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=244 Participants Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=227 Participants Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Number of Participants Identified as a Responder After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups	49 Participants	44 Participants	—

PRIMARY outcome

Timeframe: Up to Day 9

Population: Participants in the PP population, administered at least 1 dose of study drug, and had a post-randomization evaluation (mITT Population). Participants who discontinued early for reasons other than efficacy were included in the mITT population using Last Observation Carried Forward (LOCF).

Treatment comparison of the number of participants in the mITT population that were identified as responders at the end of the treatment period evaluated on Day 8 + 1 is presented. A responder was defined as a participant with at least a 25% reduction from baseline in the sum of percent basal/parabasal + percent intermediate cells on vaginal cytology and vaginal pH ≤5.0 with a change from baseline vaginal pH of at least 0.5.

Outcome measures

Outcome measures
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=267 Participants Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=262 Participants Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream n=132 Participants Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Number of Participants Identified as a Responder After Completing Study Treatment in the Generic Estradiol Vaginal Cream, Estrace Vaginal Cream, and Vehicle Vaginal Cream Groups	53 Participants	53 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 9

The number of participants in the PP population that are identified as Treatment Success at the end of the treatment period evaluated on Day 8 ± 1 is presented. A Treatment Success is defined as a score of 0 or 1 at Day 8 ± 1 for the symptom identified at baseline as the most bothersome. This evaluation was based on participant self-assessed symptoms of vulvar and vaginal atrophy on a scale of 0 to 3 where 0 = none and 3 = severe. The symptoms that were evaluated were vaginal dryness, vaginal/vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, and vaginal bleeding. Any participant who withdrew from the study because of lack of efficacy was included as a non-responder.

Outcome measures

Outcome measures
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=244 Participants Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=227 Participants Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Number of Participants Identified as Treatment Success After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups	161 Participants	153 Participants	—

SECONDARY outcome

Timeframe: Up to 9 months

The number of participants in the mITT Population that are identified as Treatment Success at the end of the treatment period evaluated on Day 8 ± 1 is presented. A Treatment Success is defined as a score of 0 or 1 at Day 8 ± 1 for the symptom identified at baseline as the most bothersome. This evaluation is to be based on participant self-assessed symptoms of vulvar and vaginal atrophy on a scale of 0 to 3 where 0 = none and 3 = severe. The symptoms that were evaluated were vaginal dryness, vaginal/vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, and vaginal bleeding.

Outcome measures

Outcome measures
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=267 Participants Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=262 Participants Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream n=132 Participants Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Number of Participants Identified as Treatment Success After Completing Study Treatment in the Generic Estradiol Vaginal Cream, Estrace Vaginal Cream, and Vehicle Vaginal Cream Groups	175 Participants	169 Participants	80 Participants

Adverse Events

Generic Estradiol Vaginal Cream USP, 0.01%

Serious events: 0 serious events

Other events: 63 other events

Deaths: 0 deaths

Estrace Vaginal Cream USP, 0.01%

Serious events: 1 serious events

Other events: 74 other events

Deaths: 0 deaths

Vehicle Vaginal Cream

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Generic Estradiol Vaginal Cream USP, 0.01% n=267 participants at risk Participants were to self-administer 2 g of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Estrace Vaginal Cream USP, 0.01% n=262 participants at risk Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.	Vehicle Vaginal Cream n=132 participants at risk Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
General disorders Device occlusion	0.00% 0/267 • Baseline up to Day 9 All participants who were randomized and administered at least 1 dose of study drug (Safety Population).	0.38% 1/262 • Baseline up to Day 9 All participants who were randomized and administered at least 1 dose of study drug (Safety Population).	0.00% 0/132 • Baseline up to Day 9 All participants who were randomized and administered at least 1 dose of study drug (Safety Population).

Other adverse events

Additional Information

Senior Director, CE Studies

Teva Pharmaceuticals USA, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.
Publication restrictions are in place

Restriction type: OTHER